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Purpose: The purpose of this study was to study the relationship between the presence of a deep lateral femoral notch sign (DLFNS) in anterior cruciate ligament (ACL)‐injured patients and a higher posterior lateral tibial slope (LPTS), a reduced meniscal bone angle (MBA), a higher LPTS/MBA ratio and a higher incidence of concomitant injuries in primary ACL tears. Methods: A retrospective case‐control study was performed in patients submitted to primary ACL reconstruction with an available preoperative magnetic resonance imaging (MRI) scan. Patients with ACL tears and a femoral impactation with a depth ≥2 mm were assorted to the DLFNS group and patients with ACL tear and without a DLFNS to the control group. LPTS and MBA were measured in MRI. The presence of concomitant injuries (meniscal, posterior cruciate ligament, medial collateral ligament, lateral collateral ligament and bone injuries) was assessed in MRI. Quantitative data are presented in the median ± interquartile range (IQR). Results: There were 206 patients included in the study, with 46 patients assorted to the DLFNS group and 160 patients to the control group. In the DLFNS group, the median LPTS was 6.7° (IQR: 4.0–8.2) versus 4.0° in the control group (IQR: 2.2–6.5) (p = 0.003). The LPTS/MBA ratio was significantly higher in the DLFNS group, with a median of 0.32 (IQR: 0.19–0.44), in comparison to the control group, with a median of 0.19 (IQR: 0.11–0.31) (p < 0.001). The multivariable logistic regression analysis showed that the LPTS is an independent risk factor to having a DLFNS (odds ratio [OR] = 1.161; 95% confidence interval [CI]: 1.042–1.293, p = 0.007). There was a higher incidence of concomitant lateral meniscal injuries in the DLFNS group (67% vs. 48%, p = 0.017). Conclusions: In patients with ACL tears, the presence of a DLFNS is associated with a steeper lateral posterior tibial slope, as well as a higher incidence of concomitant lateral meniscal injuries. Level of Evidence: Level III. [ABSTRACT FROM AUTHOR]

The association of postpartum cardiac reverse remodeling (RR) with urinary proteome, particularly in pregnant women with cardiovascular (CV) risk factors who show long-term increased risk of cardiovascular disease and mortality is unknown. We aim to profile the urinary proteome in pregnant women with/without CV risk factors to identify proteins associated with postpartum RR. Our study included a prospective cohort of 32 healthy and 27 obese and/or hypertensive and/or diabetic pregnant women who underwent transthoracic echocardiography, pulse-wave-velocity, and urine collection at the 3rd trimester and 6 months postpartum. Shotgun HPLC–MS/MS profiled proteins. Generalized linear mixed-effects models were used to identify associations between urinary proteins and left ventricle mass (LVM), a surrogate of RR. An increase in arterial stiffness was documented from 3rd trimester to 6 months after delivery, being significantly elevated in women with CV risk factors. In addition, the presence of at least one CV risk factor was associated with worse LVM RR. We identified 6 and 11 proteins associated with high and low LVM regression, respectively. These proteins were functionally linked with insulin-like growth factor (IGF) transport and uptake regulation by IGF binding-proteins, platelet activation, signaling and aggregation and the immune system's activity. The concentration of IGF-1 in urine samples was associated with low LVM regression after delivery. Urinary proteome showed a predicting potential for identifying pregnant women with incomplete postpartum RR. [ABSTRACT FROM AUTHOR]

A notable shift in understanding the human microbiome's influence on cardiovascular disease (CVD) is underway, although the causal association remains elusive. A systematic review and meta-analysis were conducted to synthesise current knowledge on microbial taxonomy and metabolite variations between healthy controls (HCs) and those with CVD. An extensive search encompassing three databases identified 67 relevant studies (2012–2023) covering CVD pathologies from 4707 reports. Metagenomic and metabolomic data, both qualitative and quantitative, were obtained. Analysis revealed substantial variability in microbial alpha and beta diversities. Moreover, specific changes in bacterial populations were shown, including increased Streptococcus and Proteobacteria and decreased Faecalibacterium in patients with CVD compared with HC. Additionally, elevated trimethylamine N-oxide levels were reported in CVD cases. Biochemical parameter analysis indicated increased fasting glucose and triglycerides and decreased total cholesterol and low- and high-density lipoprotein cholesterol levels in diseased individuals. This study revealed a significant relationship between certain bacterial species and CVD. Additionally, it has become clear that there are substantial inconsistencies in the methodologies employed and the reporting standards adhered to in various studies. Undoubtedly, standardising research methodologies and developing extensive guidelines for microbiome studies are crucial for advancing the field. [ABSTRACT FROM AUTHOR]

The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure (HF). Four cohorts were included, involving 83 metabolites and 37 metabolite ratios, measured in 1158 HF patients. Hazard ratios (HR) of 42 metabolites and 3 metabolite ratios, present in at least two studies, were combined through meta-analysis. Higher levels of histidine (HR 0.74, 95% CI [0.64; 0.86]) and tryptophan (HR 0.82 [0.71; 0.96]) seemed protective, whereas higher levels of symmetric dimethylarginine (SDMA) (HR 1.58 [1.30; 1.93]), N-methyl-1-histidine (HR 1.56 [1.27; 1.90]), SDMA/arginine (HR 1.38 [1.14; 1.68]), putrescine (HR 1.31 [1.06; 1.61]), methionine sulfoxide (HR 1.26 [1.03; 1.52]), and 5-hydroxylysine (HR 1.25 [1.05; 1.48]) were associated with a higher risk of CV events. Our findings corroborate important associations between metabolic imbalances and a higher risk of CV events in HF patients. However, the lack of standardization and data reporting hampered the comparison of a higher number of studies. In a future clinical scenario, metabolomics will greatly benefit from harmonizing sample handling, data analysis, reporting, and sharing. [ABSTRACT FROM AUTHOR]

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance. NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Purpose: Low-flow status is a mortality predictor in severe aortic stenosis (SAS) patients, including after transcatheter aortic valve implantation (TAVI) treatment. However, the best parameter to assess flow is unknown. Recent studies suggest that transaortic flow rate (FR) is superior to currently used stroke volume index (SVi) in defining low-flow states. Therefore, we aimed to evaluate the prognostic value of FR and SVi in patients undergoing TAVI. Methods: A single-centre retrospective analysis of all consecutive patients treated with TAVI for SAS between 2011 and 2019 was conducted. Low-FR was defined as < 200 mL/s and low-SVi as < 35 mL/m2. Primary endpoint was all-cause five-year mortality, analyzed using Kaplan-Meier curves and Cox regression models. Secondary endpoint was variation of NYHA functional class six months after procedure. Patients were further stratified according to ejection fraction (EF < 50%). Results: Of 489 cases, 59.5% were low-FR, and 43.1% low-SVi. Low-flow patients had superior surgical risk, worse renal function, and had a higher prevalence of coronary artery disease. Low-FR was associated with mortality (hazard ratio 1.36, p = 0.041), but not after adjustment to EuroSCORE II. Normal-SVi was not associated with survival, despite a significative p-trend for its continuous value. No associations were found for flow-status and NYHA recovery. When stratifying according to preserved and reduced EF, both FR and SVi did not predict all-cause mortality. Conclusion: In patients with SAS undergoing TAVI, a low-FR state was associated with higher mortality, as well as SVi, but not at a 35 mL/m2 cut off. [ABSTRACT FROM AUTHOR]

Gestational diabetes, affecting about 10% of pregnancies, is characterized by impaired glucose regulation and can lead to complications for health of pregnant women and their offspring. The microbiota, the resident microbes within the body, have been linked to the development of several metabolic conditions. This systematic review with meta-analysis aims to summarize the evidence on the differences in microbiota composition in pregnant women with gestational diabetes and their offspring compared to healthy pregnancies. A thorough search was conducted in the PubMed, Scopus, and Web of Science databases, and data from 21 studies were analyzed utilizing 41 meta-analyses. In the gut microbiota, Bifidobacterium and Alistipes were found to be more abundant in healthy pregnancies, while Roseburia appears to be more abundant in gestational diabetes. The heterogeneity among study findings regarding the microbiota in the meconium is considerable. The placental microbiota exhibited almost no heterogeneity, with an increased abundance of Firmicutes in the gestational diabetes group and a higher abundance of Proteobacteria in the control. The role of the microbiota in gestational diabetes is reinforced by these findings, which additionally point to the potential of microbiome-targeted therapies. To completely comprehend the interactions between gestational diabetes and the microbiome, standardizing methodologies and further research is necessary. [ABSTRACT FROM AUTHOR]

Background: Recent heart failure (HF) guidelines have re‐classified HF patients with left ventricular ejection fraction (LVEF) between 41% and 49% as HF with mildly reduced ejection fraction (HFmrEF). HFmrEF treatment is often considered a grey zone as no randomized controlled trials (RCTs) were conducted exclusively on these patients. Aims: A network meta‐analysis (NMA) was performed to compare treatment effect of mineralocorticoid receptor antagonists (MRA), angiotensin receptor neprilysin inhibitor (ARNi), angiotensin receptor blockers (ARB), angiotensin‐converting‐enzyme inhibitors (ACEi), sodium‐glucose cotransporter‐2 inhibitors (SGLT2i), and beta‐blockers (BB) in HFmrEF cardiovascular (CV) outcomes. Methods and results: RCTs sub‐analyses evaluating the efficacy of pharmacological treatment in HFmrEF patients were searched. Hazard ratios (HRs) and their variance were extracted from each RCT for (i) composite of CV death or HF hospitalizations, (ii) CV death, and (iii) HF hospitalizations. A random‐effects NMA was performed to compare and assess the treatment efficiency. Six RCTs with subgroup analysis according to participants' ejection fraction, a patient‐level pooled meta‐analysis of two RCTs, and an individual patient‐level analysis of eleven BB RCTs were included, totalling 7966 patients. To our primary endpoint, SGLT2i vs. placebo was the only comparison with significant results, with a 19% risk reduction in the composite of CV death or HF hospitalizations [HR 0.81, 95% confidence interval (CI) 0.67–0.98]. In HF hospitalizations, the impact of the pharmacological therapies was more notorious, and ARNi reduced in 40% the risk of HF hospitalizations (HR 0.60, 95% CI 0.39–0.92), SGLT2i in 26% (HR 0.74, 95% CI 0.59–0.93) and renin–angiotensin system inhibition (RASi) with ARB and ACEi in 28% (HR 0.72, 95% CI 0.53–0.98). Although BBs were globally less beneficial, they were the only class that supported a reduced risk of CV death (HR vs. placebo: 0.48, 95% CI 0.24–0.95). We did not observe a statistically significant difference in any comparison between active treatments. There was a sound reduction with ARNi on the primary endpoint (HR vs. BB: 0.81, 95% CI 0.47–1.41; HR vs. MRA 0.94, 95% CI 0.53–1.66) and on HF hospitalizations (HR vs. RASi 0.83, 95% CI 0.62–1.11; HR vs. SGLT2i 0.80, 95% CI 0.50–1.30). Conclusions: In addition to SGLT2i, pharmacological treatment recommended for HF with reduced LVEF, namely, ARNi, MRA, and BB, can also be effective in HFmrEF. This NMA did not show significant superiority over any pharmacological class. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we examined how age impacts the outcomes of breast cancer by comparing three age groups: patients 45 years old or younger, patients between 46 and 69 years old, and patients 70 years old or older. Despite similar cancer staging and tumor characteristics among the age groups, the study found that older patients were prone to suboptimal treatment. Older patients also had a lower overall survival rate, but this was not related to cancer itself. Instead, we found that undertreatment was a factor that negatively impacted survival for older women with breast cancer. This study suggests that tumor characteristics and treatment compliance are more important predictors of survival than chronological age. Age as a breast cancer (BC) prognostic factor remains debatable. Several studies have investigated clinicopathological features at different ages, but few make an age group direct comparison. The European Society of Breast Cancer Specialists quality indicators (EUSOMA-QIs) allow a standardized quality assurance of BC diagnosis, treatment, and follow-up. Our objective was to compare clinicopathological features, compliance to EUSOMA-QIs and BC outcomes in three age groups (≤45 years, 46–69 years, and ≥70 years). Data from 1580 patients with staged 0–IV BC from 2015 to 2019 were analyzed. The minimum standard and desirable target on 19 mandatory and 7 recommended QIs were studied. The 5-year relapse rate, overall survival (OS), and BC-specific survival (BCSS) were also evaluated. No meaningful differences in TNM staging and molecular subtyping classification between age groups were found. On the contrary, disparities in QIs compliance were observed: 73.1% in ≤45 years and 46–69 years women vs. 54% in older patients. No differences in loco-regional or distant progression were observed between age groups. Nevertheless, lower OS was found in older patients due to concurrent non-oncological causes. After survival curves adjustment, we underscored evidence of undertreatment impacting BCSS in ≥70 years women. Despite a unique exception—more invasive G3 tumors in younger patients—no age-specific differences in BC biology impacting outcome were found. Although increased noncompliance in older women, no outcome correlation was observed with QIs noncompliance in any age group. Clinicopathological features and differences in multimodal treatment (not the chronological age) are predictors of lower BCSS. [ABSTRACT FROM AUTHOR]

Introduction: Recurrence of atrial fibrillation (AF) within the blanking period after catheter ablation (CA) is traditionally classified as a transient and benign event. However, recent findings suggest that early recurrence (ER) is associated with late recurrence (LR), challenging the predefined "blanking period". We aimed to determine the clinical and procedural predictors of ER and LR after CA and establish the risk of LR in patients who experience ER. Methods and Results: Retrospective single‐centre study including all patients who underwent a first procedure of AF CA between 2017 and 2019. ER was defined as any recurrence of AF, atrial flutter or atrial tachycardia >30 s within 90 days after CA and LR as any recurrence after 90 days of CA. A total of 399 patients were included, 37% women, median age of 58 years [49‐66] and 77% had paroxysmal AF. Median follow‐up was 33 months (from 13 to 61). ER after CA was present in 14% of the patients, and LR was reported in 32%. Among patients who experienced ER, 84% also had LR (p <.001). Patients with ER had a higher prevalence of moderate/severe valvular heart disease, persistent AF, previous electrical cardioversion, a larger left atrium, higher coronary artery calcium score, and higher rates of intraprocedural electrical cardioversion and cardiac fibrosis on eletroanatomical mapping compared with patients without ER. After covariate adjustment, ER and female sex were defined as independent predictors of LR (hazard ratio [HR] 4.69; 95% confidence interval [CI], 2.99–7.35; p <.001 and HR 2.73; 95% CI, 1.47–5.10; p =.002, respectively). Conclusion: The risk of LR after an index procedure of CA was significantly higher in patients with ER (five‐fold increased risk). These results support the imperative need to clarify the clinical role of the blanking period. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) and the frequently coexisting aortic valve stenosis (AVS) are heart diseases accounting for most cardiac surgeries. These share many risk factors, such as age, diabetes, hypertension, or obesity, and similar pathogenesis, including endothelial disruption, lipid and immune cell infiltration, inflammation, fibrosis, and calcification. Unsuspected CAD and AVS are sometimes detected opportunistically through echocardiography, coronary angiography, and magnetic resonance. Routine biomarkers for early detection of either of these atherosclerotic-rooted conditions would be important to anticipate the diagnosis. With a noninvasive collection, urine is appealing for biomarker assessment. We conducted a shotgun proteomics exploratory analysis of urine from 12 CAD and/or AVS patients and 11 controls to identify putative candidates to differentiate these diseases from healthy subjects. Among the top 20 most dysregulated proteins, TIMP1, MMP2 and vWF stood out, being at least 2.5× increased in patients with CAD/AVS and holding a central position in a network of protein-protein interactions. Moreover, their assessment in an independent cohort (19 CAD/AVS and 10 controls) evidenced strong correlations between urinary TIMP1 and vWF levels and a common cardiovascular risk factor - HDL (r = 0.59, p < 0.05, and r = 0.64, p < 0.01, respectively). [ABSTRACT FROM AUTHOR]

Objectives: Differences in proteomic profiles between men and women may provide insights into the biological pathways that contribute to known sex differences in rheumatoid arthritis (RA). Studies focusing on sex differences in circulating proteins in RA patients are scarce. Our objective was to investigate the sex differences in circulating proteins of RA patients. Methods: Cohort study enrolling 399 RA patients. Ninety‐four circulating protein‐biomarkers (92CVDIIOlink® + troponin‐T + C‐reactive protein) were measured. Clinical, demographic, and echocardiographic characteristics were compared between men and women. Sex differences in biomarker expression were assessed using regression modeling. Results: In all, 306 (76.7%) patients were women. Compared with men, women had less visceral fat, smoked less, had diabetes and chronic obstructive pulmonary disease less frequently, and expressed more fatigue, anxiety, and depression. The association with cardiovascular outcomes did not differ between sexes. After adjusting for potential confounders, women expressed higher levels of circulating proteins related to adipokine signaling and vascular function (eg, leptin and vascular endothelial growth factor), whereas men expressed higher levels of circulating proteins related to extracellular matrix organization and inflammation (eg, matrix metalloproteinase‐2 and C‐reactive protein). These results were not found in patients without RA. Conclusion: Sex differences in circulating proteins reflect distinct pathways implicated in the pathogenesis of RA, including inflammation, adiposity, angiogenesis, and extracellular matrix organization. These findings may help further investigations into factors underlying sex‐based differences and allow future studies focused on sex‐specific personalized treatment approaches in RA. ClinicalTrials.gov ID: NCT03960515. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer (PCa) is one of the most common cancers. Due to the limited and invasive approaches for PCa diagnosis, it is crucial to identify more accurate and non-invasive biomarkers for its detection. The aim of our study was to non-invasively uncover new protein targets for detecting PCa using a proteomics and proteogenomics approach. This work identified several dysregulated mutant protein isoforms in urine from PCa patients, some of them predicted to have a protective or an adverse role in these patients. These results are promising given urine's non-invasive nature and offers an auspicious opportunity for research and development of PCa biomarkers. To identify new protein targets for PCa detection, first, a shotgun discovery experiment was performed to characterize the urinary proteome of PCa patients. This revealed 18 differentially abundant urinary proteins in PCa patients. Second, selected targets were clinically tested by immunoblot, and the soluble E-cadherin fragment was detected for the first time in the urine of PCa patients. Third, the proteogenome landscape of these PCa patients was characterized, revealing 1665 mutant protein isoforms. Statistical analysis revealed 6 differentially abundant mutant protein isoforms in PCa patients. Analysis of the likely effects of mutations on protein function and PPIs involving the dysregulated mutant protein isoforms suggests a protective role of mutations HSPG2*Q1062H and VASN*R161Q and an adverse role of AMBP*A286G and CD55*S162L in PCa patients. This work originally characterized the urinary proteome, focusing on the proteogenome profile of PCa patients, which is usually overlooked in the analysis of PCa and body fluids. Combined analysis of mass spectrometry data using two different software packages was performed for the first time in the context of PCa, which increased the robustness of the data analysis. The application of proteogenomics to urine proteomic analysis can be very enriching in mutation-related diseases such as cancer. [ABSTRACT FROM AUTHOR]

Although silver nanoparticles (AgNPs) are widely disseminated and show great potential in the biomedical field, there is a recognized need to better understand their action at the metabolic and functional levels. In this work, we have used NMR metabolomics, together with conventional clinical chemistry and histological examination, to characterize multi-organ and systemic metabolic responses to AgNPs intravenously administered to mice at 8mg/kg body weight (a dose not eliciting overt toxicity). Themajor target organs of AgNPs accumulation, liver and spleen, showed the greatestmetabolic changes, in a clear 2-stage response. In particular, the liver of dosed mice was found to switch fromglycogenolysis and lipid storage, at 6h postinjection, to glycogenesis and lipolysis, at subsequent times up to 48 h. Moreover, metabolites related to antioxidative defense, immunoregulation and detoxification seemed to play a crucial role in avoiding major hepatic damage. The spleen showed several early changes, including depletion of several amino acids, possibly reflecting impairment of hemoglobin recycling, while only a few differences remained at 48h postinjection. In the heart, the metabolic shift towards TCA cycle intensification and increased ATP production possibly reflected a beneficial adaptation to the presence of AgNPs. On the other hand, the TCA cycle appeared to be down regulated in the lungs of injected mice, which showed signs of inflammation. The kidneys showed the mildestmetabolic response to AgNPs. Overall, this study has shown that NMRmetabolomics is a powerful tool to monitor in vivo metabolic responses to nanoparticles, revealing unforeseen effects. [ABSTRACT FROM AUTHOR]

Purpose: To differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy. Methods: Two cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis. Results: Small changes were detected in the levels of some amino acids, organic acids, dimethyl sulfone and specific lipid moieties, thus providing some biochemical information on the disease. The possible confounding effects of gender, smoking history and age were assessed in each cohort and found to be minimal when compared to that of the disease. A similar observation was noted in relation to age-related comorbidities. Furthermore, partially distinct putative AMD metabolite fingerprints were noted for the two cohorts studied, reflecting the importance of nutritional and other lifestyle habits in determining AMD metabolic response and potential biomarker fingerprints. Notably, some of the metabolite changes detected were noted as potentially differentiating controls from patients diagnosed with early AMD. Conclusion: For the first time, this study showed metabolite changes in the plasma of patients with AMD as compared to controls, using NMR. Geographical origins were seen to affect AMD patients´ metabolic profile and some metabolites were found to be valuable in potentially differentiating controls from early stage AMD patients. Metabolomics has the potential of identifying biomarkers for AMD, and further work in this area is warranted. [ABSTRACT FROM AUTHOR]

Rationale Xanthones (XH) are a class of heterocyclic compounds widely distributed in nature that hold numerous noteworthy biological and antioxidant activities. Therefore, it is of utmost importance to achieve relevant detailed structural information to understand and assist prediction of their biological properties. The potential relationship between radical-mediated xanthone chemistry in the gas phase and their promising antioxidant activities has not been previously explored. Methods Protonated xanthones XH1-9 were generated in the gas phase by electrospray ionization (ESI) and the main fragmentation pathways of the protonated XH1-9 formed due to collision-induced dissociation (CID) were investigated. Results In the CID-MS/MS spectra of [M+H]+ ions of XH1, XH2 and XH4 the product ions formed due to H2O elimination corresponding to the base peak of the spectra. For the remaining six xanthones (XH3, XH5-9), showing the most promising biological profile, the product ion produced with the highest relative abundance (RA) corresponded to the one formed through concomitant loss of H2O plus CO. Indicative of an inexistent or lower biological activity is the combined loss of CO plus O unique to the CID-MS/MS spectra of XH1, XH2, XH4, and XH5. The product ion formed by loss of 64 Da (concomitant loss of two molecules of H2O plus CO) is only observed for xanthones containing a catechol unit (XH3 and XH6-9). This product ion has the highest RA for the most potent scavenger of reactive oxygen and nitrogen species XH9 that contains two of these catechol moieties. Conclusions A strong relationship between some of the biological activities of the studied 2,3-diarylxanthones and their ESI-MS/MS fragmentation spectra was found. The multivariate statistical analysis results suggest that the selected MS features are related to the important biological features. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

NMR metabolomics of lung tissues revealed distinct metabolic signatures for adenocarcinomas and squamous cell carcinomas (the two types being discriminated with a 94% classification rate), thus showing potential for aiding tumours subtyping, a critical diagnostic requirement in lung cancer management.Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through 1H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and adjacent control tissues from 56 patients undergoing surgical excision of primary lung carcinomas. Multivariate modeling allowed tumour and control tissues to be discriminated with high accuracy (97% classification rate), mainly due to significant differences in the levels of 13 metabolites. Notably, the magnitude of those differences were clearly distinct for AdC and SqCC: major alterations in AdC were related to phospholipid metabolism (increased phosphocholine, glycerophosphocholine and phosphoethanolamine, together with decreased acetate) and protein catabolism (increased peptide moieties), whereas SqCC had stronger glycolytic and glutaminolytic profiles (negatively correlated variations in glucose and lactate and positively correlated increases in glutamate and alanine). Other tumour metabolic features were increased creatine, glutathione, taurine and uridine nucleotides, the first two being especially prominent in SqCC and the latter in AdC. Furthermore, multivariate analysis of AdC and SqCC profiles allowed their discrimination with a 94% classification rate, thus showing great potential for aiding lung tumours subtyping. Overall, this study has provided new, clear evidence of distinct metabolic signatures for lung AdC and SqCC, which can potentially impact on diagnosis and provide important leads for future research on novel therapeutic targets or imaging tracers. [ABSTRACT FROM AUTHOR]

A novel approach based on headspace solid-phase microextraction (HS-SPME) combined with comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry (GC×GC–ToFMS) was developed for the simultaneous screening of microbial and mite contamination level in cereals and coffee beans. The proposed approach emerges as a powerful tool for the rapid assessment of the microbial contamination level (ca. 70 min versus ca. 72 to 120 h for bacteria and fungi, respectively, using conventional plate counts), and mite contamination (ca. 70 min versus ca. 24 h). A full-factorial design was performed for optimization of the SPME experimental parameters. The methodology was applied to three types of rice (rough, brown, and white rice), oat, wheat, and green and roasted coffee beans. Simultaneously, microbiological analysis of the samples (total aerobic microorganisms, moulds, and yeasts) was performed by conventional plate counts. A set of 54 volatile markers was selected among all the compounds detected by GC×GC–ToFMS. Principal Component Analysis (PCA) was applied in order to establish a relationship between potential volatile markers and the level of microbial contamination. Methylbenzene, 3-octanone, 2-nonanone, 2-methyl-3-pentanol, 1-octen-3-ol, and 2-hexanone were associated to samples with higher microbial contamination level, especially in rough rice. Moreover, oat exhibited a high GC peak area of 2-hydroxy-6-methylbenzaldehyde, a sexual and alarm pheromone for adult mites, which in the other matrices appeared as a trace component. The number of mites detected in oat grains was correlated to the GC peak area of the pheromone. The HS-SPME/GC×GC–ToFMS methodology can be regarded as the basis for the development of a rapid and versatile method that can be applied in industry to the simultaneous assessment the level of microbiological contamination and for detection of mites in cereals grains and coffee beans. [ABSTRACT FROM AUTHOR]

ABSTRACT Diabetic patients show a high susceptibility to oral diseases of inflammatory, catabolic and chronic nature with potential impact on saliva composition. In this study, our purpose was to characterize type 1 diabetes-induced alterations in the salivary peptidome aiming to find prospective biomarkers for type 1 diabetes oral health evaluation. Peptidomic analysis of saliva from controls ( n = 5) and type 1 diabetic patients ( n = 5) were performed by liquid chromatography followed by mass spectrometry. The proteolytic activity and metalloproteinases expression was accessed by zymography and slot blot analysis, respectively. Data evidenced a significant increase in the percentage of peptides in diabetic patients paralleled by a higher proteolytic activity, compared with healthy individuals. The nonsalivary gland protein fragments identified in saliva were mainly derived from collagen and extracellular matrix proteins, namely collagen type I. The cleavage site frequency analysis showed significant differences between healthy and type 1 diabetic individuals, highlighting the activity of proteases such as matrix metalloproteinase-9 and cathepsin D. Our results highlight salivary collagen fragments as potential biomarkers to follow up diabetes-related oral damage. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the potential of (1)H NMR spectroscopy, combined with multivariate statistics, for discriminating between tumour and non-involved (control) pulmonary parenchyma and for providing biochemical information on different histological types. Paired tissue samples from 24 primary lung tumours were directly analysed by high-resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy (500 MHz), and their spectral profiles subjected to principal component analysis (PCA) and partial least squares regression discriminant analysis (PLS-DA). Tumour and adjacent control parenchyma were clearly discriminated in the PLS-DA model with a high level of sensitivity (95% of tumour samples correctly classified) and 100% specificity (no false positives). The metabolites giving rise to this separation were mainly lactate, glycerophosphocholine, phosphocholine, taurine, reduced glutathione and uridine di-phosphate (elevated in tumours) and glucose, phosphoethanolamine, acetate, lysine, methionine, glycine, myo- and scyllo-inositol (reduced in tumours compared to control tissues). Furthermore, PLS-DA of a sub-set of tumour samples allowed adenocarcinomas to be discriminated from carcinoid tumours and epidermoid carcinomas, highlighting differences in metabolite levels between these histological types, and therefore revealing valuable knowledge on the biochemistry of different types of bronchial-pulmonary carcinomas. [ABSTRACT FROM AUTHOR]

The preparation of table olives according to the Italian traditional “Ferrandina” method (Fer) includes an initial blanching step of black Cassanese olives, followed by salting and oven-drying. Its industrial implementation, also called the “Sybaris” method (Syb), replaces the blanching procedure by cutting the olives followed by immersion in water. The measurement of tensile properties showed that the Fer processing increased the weakness, softness, and deformability of the skin and the flesh of olive fruits, while the flesh of the Syb fruits became stronger and stiffer. These differences are probably correlated to the degradation and/or reorganisation of cell wall polysaccharides in the fruits. The degradation of pectic and hemicellulosic polysaccharides in the Fer olives was inferred by their increased solubility in aqueous solutions. Contrarily, retention of pectic polysaccharides was observed in Syb olives. As no correlation was found between cell wall degrading enzymatic activities and cell wall polysaccharides extractability, it is probable that these modifications were driven by heat. [ABSTRACT FROM AUTHOR]

Native biofluid peptides offer important information about diseases, holding promise as biomarkers. Particularly, the non-invasive nature of urine sampling, and its high peptide concentration, make urine peptidomics a useful strategy to study the pathogenesis of renal conditions. Moreover, the high number of detectable peptides as well as their specificity set the ground for the expansion of urine peptidomics to the identification of surrogate biomarkers for extra-renal diseases. Peptidomics further allows the prediction of proteases (degradomics), frequently dysregulated in disease, providing a complimentary source of information on disease pathogenesis and biomarkers. Then, what does urine peptidomics tell us so far? In this paper, we appraise the value of urine peptidomics in biomarker research through a comprehensive analysis of all datasets available to date. We have mined > 50 papers, addressing > 30 different conditions, comprising > 4700 unique peptides. Bioinformatic tools were used to reanalyze peptide profiles aiming at identifying disease fingerprints, to uncover hidden disease-specific peptides physicochemical properties and to predict the most active proteases associated with their generation. The molecular patterns found in this study may be further validated in the future as disease biomarker not only for kidney diseases but also for extra-renal conditions, as a step forward towards the implementation of a paradigm of predictive, preventive and personalized (3P) medicine. [ABSTRACT FROM AUTHOR]

RCC usually develops and progresses asymptomatically and, when detected, it is frequently at advanced stages and metastatic, entailing a dismal prognosis. Therefore, there is an obvious demand for new strategies enabling an earlier diagnosis. The importance of metabolic rearrangements for carcinogenesis unlocked a new approach for cancer research, catalyzing the increased use of metabolomics. The present study aimed the NMR metabolic profiling of RCC in urine samples from a cohort of RCC patients (n = 42) and controls (n = 49). The methodology entailed variable selection of the spectra in tandem with multivariate analysis and validation procedures. The retrieval of a disease signature was preceded by a systematic evaluation of the impacts of subject age, gender, BMI, and smoking habits. The impact of confounders on the urine metabolomics profile of this population is residual compared to that of RCC. A 32-metabolite/resonance signature descriptive of RCC was unveiled, successfully distinguishing RCC patients from controls in principal component analysis. This work demonstrates the value of a systematic metabolomics workflow for the identification of robust urinary metabolic biomarkers of RCC. Future studies should entail the validation of the 32-metabolite/resonance signature found for RCC in independent cohorts, as well as biological validation of the putative hypotheses advanced. [ABSTRACT FROM AUTHOR]

An abstract of the article "NMR metabonomic study of lung cancer: metabolic profiling of urine and blood plasma," by Joana Carrola, Ana M. Gil, Brian J. Goodfellow is presented.

An abstract of the article "NMR metabonomic study of lung cancer: metabolic profiling of tissues," by Ana M. Gil, Brian J Goodfellow, Isabel M. Carreira is presented.